iRAGE AS A NOVEL CARBOXYMETHYLATED PEPTIDE THAT PREVENTS AGE-INDUCED APOPTOSIS AND ENDOPLASMIC RETICULUM STRESS IN VASCULAR SMOOTH MUSCLE CELLS
| Autor: | Maltais, Jean-Sébastien, Simard, Elie, Froehlich, Ulrike, Denault, Jean-Bernard, Gendron, Louis, Grandbois, Michel |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
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| DOI: | 10.18143/jisanh_v3i2_1010 |
| Popis: | RAGE overexpression in smooth muscle cells of vulnerable atheromatous plaques suggests a central role in their apoptosis and in diabetes-related cardiovascular events. With the goal of preventing RAGE activation, we synthesized a peptide (iRAGE) whose sequence is derived from an 11-amino acid site surrounding lysine-378, a frequently glycated binding site of carboxymethyllysine-human serum albumin (CML-HSA) in vivo. Pretreatment with iRAGE was successful to prevent RAGE signaling via NF-κB, a major contributor to chronic inflammation. Moreover, as RAGE activation induced apoptosis of more than 75.6% of smooth muscle cells stimulated with CML-HSA, the peptide inhibited RAGE-induced apoptosis and normalized the expression of Bcl-2 homologs, key regulators of the mitochondrial pathway of apoptosis. Interestingly, RAGE blockade diminished the generation of endoplasmic reticular stress, as observed by reduced formation of stress granules and lesser expression of stress marker HuR. This result is of particular interest since HuR can regulate apoptosis by increasing the expression of caspase-9, an event that is prevented by treatment with iRAGE. As activation of RAGE involves the oligomerization of the receptor, our results support the model by which iRAGE inhibits RAGE signaling by hindering the binding of multimeric ligands and by stabilizing the receptors in a monomer state. Journal of International Society of Antioxidants in Nutrition & Health, Vol 3, No 2 (2016): Journal of ISANH Volume 3: Special Issue for Maillard Reaction & Glycation |
| Databáze: | OpenAIRE |
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